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01.
Nature (Science) 2026-06-17

Confined migration induces non-lethal DNA damage in developing neurons

Authors:

Migratory cells tend to have soft nuclei that deform and penetrate narrow spaces1,2. Extensive nuclear deformation during migration can cause nuclear-envelope rupture and DNA damage in cancer cells, which may contribute to malignant transformation during tumour progression3–6. However, the importance of DNA damage in physiological migration is less well understood. Here we demonstrate that the migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-stranded breaks (DSBs) due to mechanostress during passage through narrow interstitial spaces. In contrast to many other migratory cells, these DSBs occur without detectable nuclear envelope rupture. Confined migration increases topoisomerase-IIβ covalently bound DSBs, and these lesions are repaired through non-homologous end-joining during brain development without causing cell death. Genome sequencing revealed that DSBs tend to occur at transcriptionally inactive regions. The deletion of ligase IV at the onset of neuronal migration leads to persistent DSB accumulation in cerebellar neurons with moderate transcriptional changes in genes related to synaptic function, neuronal development and stress and immune responses. The mutant mouse develops mild motor deficits in later life, suggesting that the DNA damage generated during normal brain development poses a potential disease risk if left unrepaired. The migration of neurons in developing cerebral and cerebellar cortices is accompanied by massive DNA double-strand breaks due to mechanostress during passage through narrow interstitial spaces.

02.
arXiv (CS.LG) 2026-06-15

Deep Spectral Learning of Embedded Latent Transfer Operators for Stochastic Dynamical Systems

arXiv:2606.14079v1 Announce Type: new Abstract: We propose a spectral learning method for stochastic nonlinear dynamical systems represented with embedded latent transfer operators in deep feature spaces. We instantiate the method as Deep Spectral Encoder (DSE), an operator-based latent state-space model in which a time-invariant neural encoder implements learnable nonlinear feature maps from observations, and these features define Markovian latent states whose temporal evolution and observation mapping are described by the transfer and observation operators, respectively. Functional canonical correlation analysis in a learnable Galerkin-projected feature space provides state coordinates from past and future observations, and the two linear operators are estimated on the state coordinates as ridge-regularized closed-form solutions that coincide with Galerkin projections of the associated covariance operators. On this representation, we generalize sequential Bayesian filtering and Koopman spectral mode decomposition in feature space. Experiments on several scenarios show stable and superior performance with sequential Bayesian filtering and dynamic mode decomposition baselines even under noise and partial observability.

03.
bioRxiv (Bioinfo) 2026-06-19

Accurate detection of tumor clonality and ongoing expansion mode from genomic data

Recent evidence shows that despite considerable effort, currently available algorithms for estimating intra-tumor heterogeneity (ITH) remain limited. We developed DECODE (Deciphering Cancer Origin from DNA Evolution), a novel mutation clustering method that incorporates the impact of sample-specific sequencing coverage and mutation calling biases. On synthetic data, DECODE outperformed existing methods across multiple clonality metrics and accurately detected and characterized the neutral tail in the site frequency spectrum (SFS), which encodes the tumor's ongoing expansion mode. In acute myeloid leukemia, accounting for the neutral tail enabled DECODE to yield more parsimonious clonal decompositions that align more closely with known subclonal dynamics that drive relapse. Applied to data from The Cancer Genome Atlas, DECODE not only detected a neutral SFS tail in most samples across tumor types but also uncovered a clinically meaningful link between ITH and survival in low-grade glioma. By jointly inferring clonality and expansion mode, DECODE provides two complementary and prognostically relevant readouts of tumor evolution from single tumor genomic samples.

04.
arXiv (quant-ph) 2026-06-25

Simulating Universal Quantum Gate Sets on Photonic OAM Qubits: Single-Qubit and Multi-Qubit Operations via Spatial Light Modulator Phase Holography

arXiv:2606.26088v1 Announce Type: new Abstract: Spatial light modulators (SLMs) have emerged as reconfigurable platforms for photonic quantum information processing, offering software-defined control over the orbital angular momentum (OAM) of light encoded in Laguerre-Gaussian (LG) beams. This paper presents a comprehensive simulation and hardware-grounded fidelity analysis of quantum gate operations implemented on the HOLOEYE LC 2012 transmissive SLM. A realistic three-channel noise model comprising 8-bit quantisation noise, twisted-nematic (TN) electronic and thermal noise, and phase-wrap clipping error is obtained from the manufacturer's datasheet without free-parameter fitting, yielding a total noise of $\sigma_{total} = 92.4mrad$. The complete universal single-qubit gate set $\{X, Y, Z, S, T, H\}$ and two-qubit entangling gates $\{CNOT, CZ, SWAP\}$ are simulated on a $512 \times 512$ computational grid. Results show that predicted gate fidelity are in the range of $F = 0.9914–0.9936$, with fork grating gates limited primarily by TN noise and phase gates achieving higher fidelity owing to zero phase-wrap clipping error. In addition, Bell state preparation via the H-CNOT circuit achieves $F(\Phi^+) = 0.9914$ after two SLM interactions. We benchmark our obtained results against six published experimental studies spanning the 78%–99.6% fidelity range. Finally, a wavelength-dependent analysis identifies 450–532 nm operation as the optimal regime for this device.

05.
arXiv (CS.CV) 2026-06-17

Training LLMs with Reinforcement Learning over Digital Twin Representations for Reasoning-Intensive Surgical VideoQA

Surgical video question answering requires multi-step reasoning across semantic, spatial, and temporal dimensions. Existing methods architecturally compress videos into discrete token representations and couple visual perception with reasoning. This approach fragments continuous spatial-temporal relationships and has been shown to restrict multi-step reasoning capabilities. We introduce a reinforcement learning (RL) framework that trains large language models (LLMs) to decouple perception from reasoning by operating over digital twin representations constructed from surgical foundation models. Additionally, we introduce hierarchical representations across frame, temporal window, and procedure levels with probabilistic uncertainty estimates. Finally, we propose a novel reward that combines format validation with accuracy assessment through clinical plausibility evaluation and uncertainty-aware calibration for training. To demonstrate the capabilities of this approach, we introduce REAL-Colon-Reason, a colonoscopic benchmark with 2000 question-answer pairs across three complexity levels. We achieve state-of-the-art performance on REAL-Colon-Reason and two existing surgical VideoQA benchmarks REAL-Colon-VQA and EndoVis18-VQA.

06.
arXiv (CS.CV) 2026-06-25

LastAct: Trajectory-Guided Latest-Activity Localization for Real-Time Smart-Home Activity Recognition

Human Activity Recognition (HAR) from ambient sensors enables smart-home applications such as health monitoring and assisted living. In realistic deployments, however, sensor events arrive as a continuous stream and activity boundaries are unknown. Sliding-window inference therefore produces many windows that straddle transitions and contain mixed activities, creating boundary contamination that violates the pre-segmented instance assumption used by most benchmarks and models. Moreover, many pipelines under-use spatial context by treating sensor IDs as independent tokens. We present LastAct, a trajectory-centric framework for streaming smart-home HAR that targets the most recent activity under mixed windows while explicitly modeling spatial structure. LastAct projects sensor events onto the home floorplan to form a layout-aligned trajectory image sequence that preserves spatial continuity. A lightweight gate identifies contaminated windows, and a boundary localizer estimates the last transition to enable boundary-guided masking that emphasizes post-boundary evidence and suppresses stale context. For efficiency, we reuse a precomputed layout-aligned template cache to avoid repeated rendering. Empirically, across four public smart-home datasets under near-realistic mixed-activity protocols, LastAct achieves competitive or superior performance on pure windows and yields substantial Macro-F1 gains on cross/mixed windows, demonstrating improved robustness under near-realistic sliding-window regimes.

07.
medRxiv (Medicine) 2026-06-17

High burden of subclinical TB in Africa revealed from a postmortem cohort.

Tuberculosis (TB) is increasingly recognised as a spectrum of infection and disease, yet the prevalence of viable, asymptomatic Mycobacterium tuberculosis (M.tb) infection remains uncertain. Subclinical Tuberculosis (scTB), defined as microbiologically confirmed M.tb infection in the absence of recognised symptoms, is under detected by symptom, sputum and imaging-based approaches. We conducted postmortem examinations of 94 adults who died from non-infectious causes, none of whom were clinically suspected of TB or reported TB related symptoms prior to death. Lung and extrapulmonary tissues were cultured for M.tb. Viable M.tb was confirmed in six individuals, corresponding to a prevalence of 6.4% (95% CI: 2.4 to 13.4%). These findings provide direct tissue-based evidence that viable, asymptomatic M.tb infection can persist beyond the reach of conventional clinical detection. Our data suggest that a biologically active reservoir of infection may exist undetected within high-burden settings, with implications for surveillance strategies aimed at TB elimination.

08.
arXiv (CS.CL) 2026-06-17

Reading between the Lines: Leveraging Large Language Models for Global Dementia and Depression Assessment from Clinical Interviews

Dementia and depression are the most prevalent neuropsychiatric disorders in geriatric populations, and their overlapping symptoms pose major challenges for differential diagnosis. In this study, we investigate open-weights Large Language Models (LLMs) for predicting dementia and depression severity from speech samples collected during standardized history taking interviews with 154 German-speaking subjects. We introduce an observer-based Global Depression Scale (GDS-D) aligned with the established Global Deterioration Scale (GDS), enabling parallel global staging of affective and cognitive symptoms. We compare three LLMs (Mistral 3.1, DeepHermes, Qwen3) in two settings: (1) zero-shot prediction and (2) LLM-based feature extraction for Support Vector Regression, using human and pause-enriched transcripts. Results show that LLMs effectively predict depression severity in zero-shot settings (best MAE of 0.60), while dementia assessment benefits substantially from structured feature extraction (best MAE of 0.78), reducing errors by up to 35% over zero-shot baselines. Pause-enriched transcripts achieve competitive performance with human transcriptions, demonstrating the viability of fully automatic screening pipelines for differential neuropsychiatric assessment.

09.
medRxiv (Medicine) 2026-06-22

Referral pathways, ETAT triage acuity, and inpatient outcomes among children presenting to a national tertiary paediatric emergency unit in Ghana: a prospective cohort study

Emergency referral systems in sub-Saharan Africa are fragmented, and children reaching tertiary facilities through different referral pathways often arrive in advanced clinical states. Prospective data simultaneously characterising referral patterns, triage acuity at presentation, diagnostic case mix, and inpatient mortality at a national tertiary paediatric emergency unit are lacking from West Africa. This prospective cohort study enrolled 675 consecutively presenting children aged one month to 12 years at the Paediatric Emergency Unit of Korle Bu Teaching Hospital, Accra, Ghana, from February to December 2019. The primary outcome was all-cause inpatient mortality. Key variables collected included referral status and facility tier, Emergency Triage Assessment and Treatment (ETAT) triage category, ICD-10 diagnostic classification, Oyedeji socioeconomic classification, and time from symptom onset to PEU registration. Crude odds ratios were computed for all candidate predictors. Multivariable logistic regression was conducted using complete case analysis (n = 613). Of 675 children, 63.0% (n = 425) were referred from another health facility; referred children had higher ETAT emergency triage category rates than self-presenting children (32.7% vs 27.6%, p < 0.001). Overall inpatient mortality was 9.9% (67/675). Mortality varied by referral source: 16.7% among secondary/regional hospital referrals, 11.0% among lower-tier facility referrals (district, municipal, CHAG, polyclinic, private, health centre, and maternity home facilities combined, n = 356), 7.6% among self-presenting children, and 7.4% among tertiary referrals. Overall, 30.8% of children were classified as ETAT emergencies on arrival, with case fatility rate of 21.6%. The three most common diagnostic domains were respiratory conditions (17.2%), blood and haematological disorders (17.0%), and digestive presentations (16.4%). Inpatient mortality was highest in neoplastic disease (33.3%, n = 30) and circulatory presentations (31.0%, n = 29). In the primary multivariable analysis (n = 613, 51 events; events-per-variable ratio 4.2), no referral tier was independently associated with inpatient mortality after adjustment. Referral from secondary/regional hospitals showed a borderline non-significant association (adjusted odds ratio 3.09, 95% CI 0.96 to 9.90, p = 0.058). School going children (60-119 months) had higher odds of inpatient death than infants (adjusted odds ratio 5.56, 95% CI 1.16 to 26.53, p = 0.032), as did adolescents (adjusted odds ratio 10.01, 95% CI 2.15 to 46.69, p = 0.003). ETAT emergency category and lower socioeconomic status were not independently significant in this model. A pre-specified sensitivity analysis using the full analytic cohort (n = 674, events-per-variable ratio 6.7) with collapsed referral categories did not confirm any referral tier association; ETAT emergency category and lower SES were independently associated in the sensitivity model. All multivariable estimates should be regarded as exploratory. This prospective cohort provides simultaneous characterisation of referral patterns, ETAT triage acuity, diagnostic case mix, and inpatient mortality at a national tertiary paediatric emergency unit in West Africa. The referral-mortality gradient and high ETAT emergency category proportion document the severity of illness arriving through different referral pathways at this facility. The association between secondary/regional hospital referral and inpatient mortality is hypothesis-generating and requires replication in an adequately powered multicentre study before any service-level conclusions can be drawn.

10.
arXiv (CS.AI) 2026-06-15

Learning What to Predict: Downstream-Guided Task Design for Continued Pretraining

arXiv:2601.22108v2 Announce Type: replace-cross Abstract: Continued pretraining is optimized with fixed self-supervised tasks but selected by downstream performance, creating a coarse feedback loop in which practitioners evaluate checkpoints, change data mixtures or objectives, and restart runs, while individual updates remain blind to target capabilities. We ask whether a small set of verifiable downstream examples can provide step-level feedback without directly supervising the learner. We introduce V-pretraining, which decouples a learner trained only with a self-supervised loss from a lightweight task designer that constructs targets or views for unlabeled batches. Given the current learner and batch, V-pretraining scores a candidate construction by predicting the first-order reduction in downstream loss after the induced self-supervised update. The designer maximizes this value; the learner then applies the update with targets or views detached, so downstream labels never update learner parameters. We instantiate V-pretraining as adaptive top-K soft targets for language modeling and learned views or masks for self-supervised vision. Across both modalities, V-pretraining improves target capabilities without degrading generalization. Under wall-clock-matched continued pretraining, it improves GSM8K Pass@1 for Qwen models using 1,024 GSM8K examples only as feedback, including a +7.4 point single-run gain for Qwen2.5-0.5B. In vision, it improves DINOv3 transfer to ADE20K semantic segmentation and NYUv2 depth estimation while preserving ImageNet linear accuracy, suggesting that feedback-guided task construction can improve target capabilities without collapsing general-purpose representations.

11.
arXiv (CS.AI) 2026-06-11

MPC-Patch-Bench: Security-Aware LLM Code Patch for Multi-Party Computation

arXiv:2606.11416v1 Announce Type: cross Abstract: Repository-level benchmarks for evaluating Large Language Model (LLM) code repair on Secure Multi-Party Computation (MPC) software do not yet exist, and directly transplanting general-purpose benchmarks such as SWE-bench fails on three structural fronts: (i) MPC repositories are dominated by generic Python infrastructure rather than cryptographic logic; (ii) high-value MPC fixes lack the standardized tests rigid extraction pipelines require; and (iii) standard fail-to-pass evaluation is insufficient for code that must also be cryptographically safe. MPC is increasingly deployed for privacy-preserving machine learning, biomedical collaboration, and secure analytics. Existing MPC-specific code-synthesis efforts cover only operator-level or single-framework tasks; evaluating LLM agents on real repository-level MPC repair instead demands MPC-aware data curation and a verifier matched to the security and numerical-fidelity guarantees MPC programs must obey neither of which existing benchmarks provide. We introduce MPC-Patch-Bench, a repository-level benchmark organised around two frameworks. (1)The Data Curation Framework combines a domain-specific curation agent that filters raw pull requests through three cryptographic layers with a human-AI completion engine that synthesizes missing problem statements and Fail-to-Pass/Pass-to-Pass tests, yielding 205 fully verified instances. (2)The MPC Verifier provides dedicated security and numerical-fidelity checks via dynamic differential testing against plaintext oracles and MPC-specific static analysis rules that flag unsafe reveals, insecure arithmetic, and illegal public/private casts. The strongest evaluated LLM functionally resolves only 22.9% of MPC-Patch-Bench tasks; the MPC Verifier further reduces verified resolution to 17.1%, with up to 40% of functionally-passing patches rejected for cryptographic or numerical-fidelity violations.

12.
arXiv (CS.CL) 2026-06-19

Towards Truly Multilingual ASR: Generalizing Code-Switching ASR to Unseen Language Pairs

Automatic Speech Recognition (ASR) has become a key technology for human–AI interaction. However, code-switching ASR (CS-ASR) remains particularly challenging due to the severe scarcity of multilingual CS speech resources across diverse language pairs. Existing approaches primarily improve CS-ASR performance through synthetic CS speech generation or pair-specific fine-tuning on limited bilingual datasets. Nevertheless, these approaches face an inherent scalability limitation, as support for CS must be developed separately for language pairs whose number grows combinatorially with the number of supported languages. In this work, we investigate whether CS capabilities learned from a limited set of seen language pairs can generalize to unseen language pairs through model merging and domain generalization methods. Our experiments show that merged bilingual CS-ASR models modestly generalize to unseen language pairs, suggesting limited transfer of bilingual CS capabilities across language pairs.

13.
arXiv (CS.CV) 2026-06-16

Prompt Disentanglement via Language Guidance and Representation Alignment for Domain Generalization

Domain Generalization (DG) seeks to develop a versatile model capable of performing effectively on unseen target domains. Notably, recent advances in pre-trained Visual Foundation Models (VFMs), such as CLIP, have demonstrated considerable potential in enhancing the generalization capabilities of deep learning models. Despite the increasing attention toward VFM-based domain prompt tuning within DG, the effective design of prompts capable of disentangling invariant features across diverse domains remains a critical challenge. In this paper, we propose addressing this challenge by leveraging the controllable and flexible language prompt of the VFM. Noting that the text modality of VFMs is naturally easier to disentangle, we introduce a novel framework for text feature-guided visual prompt tuning. This framework first automatically disentangles the text prompt using a large language model (LLM) and then learns domain-invariant visual representation guided by the disentangled text feature. However, relying solely on language to guide visual feature disentanglement has limitations, as visual features can sometimes be too complex or nuanced to be fully captured by descriptive text. To address this, we introduce Worst Explicit Representation Alignment (WERA), which extends text-guided visual prompts by incorporating an additional set of abstract prompts. These prompts enhance source domain diversity through stylized image augmentations, while alignment constraints ensure that visual representations remain consistent across both the original and augmented distributions. Experiments conducted on major DG datasets, including PACS, VLCS, OfficeHome, DomainNet, and TerraInc, demonstrate that our proposed method outperforms state-of-the-art DG methods.

14.
arXiv (CS.CL) 2026-06-11

Doc-to-Atom: Learning to Compile and Compose Memory Atoms

Long input sequences are central to document understanding and multi-step reasoning in Large Language Models, yet the quadratic cost of attention makes inference both memory-intensive and slow. Context distillation mitigates this by compressing contextual information into model parameters, and recent work such as Doc-to-LoRA amortizes context distillation into a single forward pass that generates one LoRA adapter per document. However, producing a single monolithic adapter for all queries leads to irrelevant-query interference, limited compositional recall, and poor scalability to long-document reasoning. To address these challenges, we propose Doc-to-Atom (Doc2Atom), a compositional parametric memory framework that decomposes each document into semantically typed knowledge atoms. Each atom is compiled into an independent micro-LoRA adapter and a provenance retrieval key. At inference time, a lightweight query router selects and assembles only the relevant atoms into a query-specific adapter, which is then injected into a frozen base model. The entire system is trained end-to-end through a multi-objective distillation framework. Experiments on six diverse QA benchmarks demonstrate that Doc2Atom outperforms Doc-to-LoRA baselines while reducing the memory cost of document internalization.

15.
arXiv (quant-ph) 2026-06-19

GPU-accelerated semidefinite programming for causal games

arXiv:2606.20519v1 Announce Type: new Abstract: The process matrix formalism describes quantum correlations in scenarios without a fixed causal order between local laboratories. Operational signatures of such correlations can be investigated through causal games. A paradigmatic example is the Guess-Your-Neighbour's-Input game, in which two parties attempt to guess each other's inputs. Correlations compatible with any definite, or probabilistically mixed, causal order cannot achieve a winning probability exceeding $1/2$. The best process-matrix strategy currently known attains a value of approximately $0.6218$ using local dimension $d=5$, while the strongest known dimension-independent upper bound is $0.7592$. In this work, we investigate whether increasing the local dimension beyond $d = 5$ can narrow this gap. To this end, we employ a see-saw optimization scheme in which each step is formulated as a semidefinite program. For scalability, we develop a custom implementation of the SCS solver in which the dominant computational cost, the projection onto the positive-semidefinite cone, is offloaded to a GPU, yielding a six-fold speedup. Using this implementation, we explore local dimensions up to $d = 8$, and we do not find significant improvements over the value at $d=5$. Our results suggest that either qualitatively different strategies are required to approach the known upper bound, or that the bound itself is not tight.

16.
arXiv (CS.CL) 2026-06-19

From Construction to Injection: Edit-Based Fingerprints for Large Language Models

Reliable model fingerprints are essential for protecting large language models (LLMs) against unauthorized redistribution and commercial misuse. In black-box deployment, verification is hindered by defensive filtering of suspected fingerprint queries, as well as by downstream model modifications that may weaken embedded ownership evidence. These risks require fingerprints to be robust in both construction and injection. For construction, prior paradigms face an imperceptibility trade-off: natural-language fingerprints may be accidentally activated, whereas garbled fingerprints are statistically exposed and easier to filter. For injection, existing methods struggle to preserve persistent trigger–target behaviors under model modification. We propose an end-to-end injected fingerprinting framework to address these challenges. Code-mixing Fingerprints (CF) use lowest-perplexity code-mixing under a high-complexity constraint to mitigate this two-sided imperceptibility trade-off. Multi-Candidate Editing (MCEdit) constructs structurally redundant, margin-separated trigger–target mappings to enable graceful degradation under model modification. Extensive evaluations on imperceptibility, detectability, and harmlessness demonstrate robust ownership verification with negligible impact on utility.

17.
arXiv (quant-ph) 2026-06-16

Degeneracy Cannot Violate the Quantum Hamming Bound

arXiv:2606.15558v1 Announce Type: new Abstract: The quantum Hamming bound is the standard finite-length sphere-packing bound for exact correction of arbitrary qubit errors. Whether degeneracy can evade this bound has remained unresolved in full generality for nearly three decades: distinct correctable errors may act identically on the code space, so the usual disjoint-sphere argument breaks down. We prove that every exact binary quantum subspace code with $K>1$ obeys the bound, without assuming either nondegeneracy or additivity. Our proof turns the Li–Xing linear-programming polynomial into an exact intersection count for quaternary Hamming balls. Monotonicity in block length and in ball-center separation then reduces the problem to a local node–edge charging inequality at the shortest admissible length. Thus degeneracy can merge correctable error sectors, but cannot enlarge the finite-length binary Hamming bound.

18.
arXiv (CS.CV) 2026-06-15

HiLo-Token: Input-Adaptive High-Low Frequency Token Compression for Efficient Image Editing

Creative image editing tools, such as Photoshop's Remove or Generative Fill buttons, are central to everyday customer use and account for a major share of traffic in Photoshop and Lightroom. However, current generative AI models face significant latency challenges, which become even more pronounced when transitioning from convolution-based U-Nets to Diffusion Transformers (DiTs). In our evaluation on hundreds of representative image editing samples spanning a wide range of mask ratios, the DiT module alone accounts for an average of 73% of the total model latency, even after being distilled from 50 timesteps down to 8 timesteps. To tackle this challenge, we propose $HiLo-Token$, an input-adaptive token compression framework that allocates more token budget to high-frequency, rich-context regions while assigning fewer tokens to low-frequency areas. Specifically, for the editing region specified by the user mask, we retain all tokens within a dilated mask to preserve strong locality and contextual relevance. Outside the editing region, we introduce a simple yet effective high-frequency token selection strategy based on spatial frequency to capture important local details, while using tokens from a 16x downsampled image to represent low-frequency components and preserve the blurry but global structure. Extensive experiments on production-level evaluation data validate the effectiveness of the proposed method, achieving 3.13x, 2.59x, and 1.67x DiT speedups on A100-80GB for image editing tasks across small, medium, and large mask ratio categories with average ratios of 6.38%, 15.92%, and 35.36%, respectively, without any regression in generation quality.

19.
arXiv (CS.AI) 2026-06-24

Representation Interventions Enable Lifelong Knowledge Memory Control in LLMs

arXiv:2511.20892v4 Announce Type: replace Abstract: Large language models (LLMs) often produce incorrect or outdated content after being employed. Efficient and accurate knowledge updates without costly retraining are a major challenge. This problem is particularly challenging in lifelong settings, where complex, unstructured knowledge must coexist without interference. We introduce RILKE (Representation Intervention for Lifelong KnowledgE Control), a robust and scalable method that treats knowledge control as interventions within the model's representation space. Leveraging representation-space expressiveness, we identify two key properties enabling RILKE to achieve fine-grained control over complex, unstructured knowledge while maintaining general utility with frozen base weights. During training, RILKE learns paraphrase-robust and edit-localized modules that limit each update to a low-dimensional subspace to minimize cross-edit interference. At inference, a query-adaptive router selects the appropriate module to guide the model's generation. Across LLaMA and Qwen models, RILKE scales effectively to large-scale benchmarks, demonstrating high edit success and strong paraphrase generalization while preserving general utility with modest memory overhead. These results show RILKE is an effective and scalable solution for lifelong knowledge control in LLMs.

20.
arXiv (CS.CL) 2026-06-11

Teaching Diffusion to Speculate Left-to-Right

Large language models (LLMs) achieve remarkable performance across a wide range of tasks, but their autoregressive decoding process incurs substantial inference costs due to inherently sequential token generation. Speculative decoding addresses this bottleneck by employing a lightweight draft model to propose multiple future tokens that are subsequently verified in parallel by a larger target model. Recent work has demonstrated that diffusion language models are well suited for this setting, as they can generate entire blocks of draft tokens in parallel and thereby alleviate the sequential constraints of autoregressive drafting. A subtlety of this regime is that block-diffusion drafters generate tokens bidirectionally within a block, whereas verification is performed by an autoregressive target model that evaluates tokens in a strictly left-to-right manner, leaving a gap between the symmetric training-time objective and the asymmetric verification-time reward. In this work, we offer an empirical analysis of three training-time interventions that narrow this gap: token positional weighting, a first-error focal loss that targets the position that breaks the accepted prefix within each block, and a chain loss term that substitutes a differentiable surrogate for the expected accepted length. The three interventions act along orthogonal axes (position, block-conditional first error, joint prefix) and compose additively; they are likewise orthogonal to test-time alignment mechanisms such as multi-draft self-selection, with which they can in principle be combined. Across four target models and six reasoning, code, and dialogue benchmarks, the three interventions raise accepted draft length by 21-76% per benchmark over a position-uniform baseline, without adding additional forward passes and without changing the inference pipeline or the rejection-sampling exactness contract.

21.
arXiv (CS.AI) 2026-06-16

Synthetic Counteradaptation: A Principle of Human-AI Co-evolution

arXiv:2606.15503v1 Announce Type: new Abstract: In this paper, we introduce the concept of synthetic counteradaptation, a process where human and AI systems co-evolve by adapting to each other's strategies and behaviors. Synthetic counteradaptation occurs when AI systems develop novel strategies or social protocols, prompting humans to extract insights and adapt their own behaviors in response, leading to the emergence of new agent interaction dynamics. To illustrate these dynamics, we analyze examples from various contexts, including the game of Go, mixed-motive social interactions, and geopolitical simulations. By exploring these cases, we demonstrate how synthetic counteradaptation provides a framework for understanding the recursive and co-evolutionary nature of human-AI interactions in multi-agent environments.

22.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

23.
arXiv (CS.CV) 2026-06-25

Geometry-Anchored Transport Framework for Exemplar-Free Class-Incremental Learning

Exemplar-free class-incremental learning (EFCIL) requires stable decision boundaries within a shifting feature space. While maintaining class-conditional Gaussian statistics provides a principled classification strategy, these parametric summaries remain sensitive to anisotropic representation drift. Existing methods often transport these statistics across tasks using a decoupled, post-hoc paradigm: optimizing a backbone without explicit geometric constraints can distort the legacy manifold, limiting the precision of retroactive alignment. In this paper, we formulate feature transport as an endogenous training constraint rather than a separate post-task step, presenting the Geometry-Anchored Transport Framework. First, we derive an Analytic Geometric Anchor via Mahalanobis-aligned regression to mitigate macroscopic anisotropic drift. Second, we introduce a Topology-Aware Evolution objective that regularizes localized manifold degradation while calibrating a residual network against the analytic prior. By coupling manifold evolution with transport constraints during the primary training phase, our framework mitigates evaluation errors without requiring decoupled fine-tuning. Experiments across CIFAR-100, TinyImageNet, and ImageNet-100 demonstrate that the proposed framework consistently improves upon existing post-hoc alternatives under strict exemplar-free constraints.

24.
arXiv (CS.AI) 2026-06-19

Interpreting Neural Combinatorial Optimization via Evolving Programmatic Bottlenecks

arXiv:2606.19741v1 Announce Type: new Abstract: Neural Combinatorial Optimization (NCO) achieves strong performance, yet its black-box nature remains a key roadblock to deployment and scientific diagnosis. Standard interpretability tools, such as Concept Bottleneck Models (CBMs), are ill-equipped for NCO, whose decisions are dynamic, state-dependent, and lack proper concept vocabulary definition. To close this gap, we introduce Evolving Programmatic Bottlenecks (EPB), to our knowledge, the first framework for interpreting NCO policies by distilling black-box NCO models into human-readable program portfolios. EPB employs an LLM to autonomously evolve a bank of programs, where each program's per-step action distribution serves as the bottleneck. EPB works through an iterative framework: Block I fixes program bank capacity and introduces a hybrid textual-numerical gradient descent scheme that couples numerical gradients for student router updates and textual gradients for LLM-based program revision; Block II dynamically adapts bank capacity via fault-targeted expansion and redundancy pruning. Extensive experiments demonstrate EPB's effectiveness and broad applicability, where the distilled program portfolios largely match original performance. EPB also reveals that NCO behavior shifts across optimization stages and can be approximated as a composition of classic heuristic variants. Our work advances interpretable NCO and establishes EPB as a promising tool for interpreting sequential decision-making models.

25.
arXiv (CS.CV) 2026-06-15

PhysVLA: Towards Physically-Grounded VLA for Embodied Robotic Manipulation

Vision-Language-Action (VLA) models excel at mapping visual inputs and natural language instructions directly to robotic control policies. However, because they are trained primarily to fit behavioural demonstration data, they do not explicitly enforce fundamental physical principles such as rigid-body dynamics or contact constraints. This exposes a critical physics gap: standard temporal smoothing applied on top of single-step or chunked VLAs trades trajectory quality for added failures that short-term memory cannot resolve. To bridge this gap, we introduce PhysVLA (Physics-VLA), a plug-and-play, inference-time framework designed to wrap any frozen VLA backbone without retraining, fine-tuning, or weight access, with less than 1 ms of overhead per control step. PhysVLA intercepts the predicted control action, captures only the simulator or system state, and applies a dual-layered correction: (i) a phase-aware finite-state machine that structures discrete task segments (approach, grasp, transport, and place), and (ii) a selective Euler-Lagrange gate that activates only when a dynamics oracle detects kinodynamic inconsistency. Evaluated across OpenVLA, OpenVLA-OFT, Force-VLA, and Generalist-VLA on LIBERO-Spatial with a 7-DoF Franka Panda, the framework delivers absolute success rate increases of up to 17% and stability increases of up to 19% with no per-task regressions, improves trajectory efficiency by up to 15% across all four backbones, and shows up to a 10x improvement in trajectory jerk robustness on a Robosuite Lift cross-simulator sweep. We further validate the framework on a real Agilex Piper arm with a pick-and-place task, confirming that PhysVLA transfers to physical hardware without retraining, with success-rate improvements of up to 50%, establishing physical awareness as a composable, backbone-agnostic runtime module.